Schlafen家族蛋白在肿瘤和病毒感染中的研究进展

doi:10.16288/j.yczz.19-311

遗传 ›› 2020, Vol. 42 ›› Issue (5): 444-451.doi: 10.16288/j.yczz.19-311

Schlafen家族蛋白在肿瘤和病毒感染中的研究进展

陈淑敏, 马铃, 岑山()

中国医学科学院北京协和医学院医药生物技术研究所免疫生物学室,北京 100050

收稿日期:2019-12-05 修回日期:2020-04-28 出版日期:2020-05-20 发布日期:2020-05-07
通讯作者: 岑山 E-mail:shancen@imb.pumc.edu.cn
作者简介:陈淑敏,在读博士研究生,专业方向：SLFN蛋白抑制HIV-1机制研究。E-mail: chenshumin1993@163.com
基金资助:
中国医学科学院医学与健康科技创新工程项目资助编号(2018-I2M-3-004 SC)

Progress of SLFN family proteins in tumor and virus infection

Shumin Chen, Ling Ma, Shan Cen()

Author Affiliation: Department of Immunology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Union Medical College, Beijing 100050, China

Received:2019-12-05 Revised:2020-04-28 Online:2020-05-20 Published:2020-05-07
Contact: Cen Shan E-mail:shancen@imb.pumc.edu.cn
Supported by:
Supported by CAMS innovation fund for Medical Sciences No(2018-I2M-3-004 SC)

摘要/Abstract

摘要：

Schlafen (SLFN)家族基因是在人类与小鼠中首先被发现的具有调控细胞生长及T细胞分化等诸多生物学功能的重要基因。该家族基因在小鼠、马和人等各个物种中广泛存在并具有较高的同源性。研究表明,SLFN蛋白在抑制细胞增殖、驱动减数分裂、调控造血细胞、下调血小板数量及调节免疫应答等方面均起到重要的作用,同时还可抑制HIV-1和流感等病毒复制。此外,SLFN蛋白还被发现与肿瘤的治疗密切相关,可以作为预测肿瘤发展进程和化疗敏感性的分子标记。本文介绍了SLFN家族蛋白的分类、结构和主要特征、定位与功能,重点综述了其在肿瘤和病毒感染等相关领域的研究进展,以期为SLFN蛋白新功能的探究提供新思路,对蛋白发挥作用的可能机制给予提示,并为各相关领域的研究提供参考。

关键词: Schlafen, 细胞生活周期, 肿瘤, 病毒

Abstract:

Schlafen (SLFN) family genes were initially found in humans and rats to regulate cell growth and T cell differentiation, and exist widely in mice, horses, humans and other species and exhibit high homology. Lines of evidence suggest that SLFN proteins play important roles in inhibiting cell proliferation, promoting meiosis, regulating hematopoietic cells, reducing platelet numbers and the immune response, and also exert antiviral functions against several virus species including HIV-1, influenza virus and others. In addition, SLFN proteins have also been found to be closely related to cancer therapy, and act as a molecular marker to predict tumor development and the sensitivity to chemotherapy drugs. In this review, we discuss the classification, structures, characteristics, location and functions of SLFN family proteins, and focus on progress related to tumor and virus infection, aiming to provide new thoughts on exploration of SLFN protein functions and the underlying mechanisms.

Key words: Schlafen, cell proliferation, tumor, virus

陈淑敏, 马铃, 岑山. Schlafen家族蛋白在肿瘤和病毒感染中的研究进展[J]. 遗传, 2020, 42(5): 444-451.

Shumin Chen, Ling Ma, Shan Cen. Progress of SLFN family proteins in tumor and virus infection[J]. Hereditas(Beijing), 2020, 42(5): 444-451.

图/表 3

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SLFN	对肿瘤细胞的影响	参考文献
m-SLFN2	抑制肿瘤细胞转移;激活c-Jun、NFATc1蛋白表达,诱导破骨细胞癌变;抑制黑色素瘤细胞增殖	[24,25,29]
m-SLFN3	抑制CSC增殖分化,提高结肠癌细胞对抗肿瘤药物敏感性	[30]
h-SLFN5	抑制黑色素瘤细胞锚定依赖生长;胃癌细胞高表达,可作为胃癌发展过程组织学诊断标志	[13,26]
h-SLFN11	靶向剪切胞内ATR/ATM蛋白翻译所需tRNA,提高肿瘤细胞对电离辐射、拓扑异构酶抑制剂以及DDA敏感性,促进肿瘤细胞周期停滞和凋亡	[31~35]
h-SLFN12	SLFN12-PDE3A复合物下调胞内Bcl-2和Mcl-1蛋白水平,靶向诱导PDE3A高表达肿瘤细胞凋亡	[27,28,36,37]

SLFN	对病毒的影响	参考文献
h-SLFN11	识别HIV-1密码子偏好性,抑制HIV-1病毒复制; 下调宿主细胞tRNA丰度,选择性抑制单正链RNA病毒(WNV、DENV和ZIKV等)复制	[17,38,39]
h-SLFN12	抑制HIV-1、EIAV、HERV-K、MLV及PFV等逆转录病毒复制	[40]
h-SLFN13	选择性地剪切病毒RNA,抑制HIV-1;抑制ZIKV病毒复制	[20]
h-SLFN14	增强IFN抗病毒活性,抑制流感病毒复制;抑制HIV病毒复制	[41]

Schlafen家族蛋白在肿瘤和病毒感染中的研究进展

Progress of SLFN family proteins in tumor and virus infection

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